1. Field of the Invention
The present invention relates to the microbiology industries, and more particularly, to a method of producing carboxylic acid by fermentation. The present invention also relates to the microorganism which is used in the production method
2. Brief Description of the Related Art
L-amino acids such as L-lysine, L-glutamic acid, L-threonine, L-leucine, L-isoleucine, L-valine, and L-phenylalanine are industrially produced by fermentation using microorganisms belonging to the genus Brevibacterium, Corynebacterium, Bacillus, Escherichia, Streptomyces, Pseudomonas, Arthrobacter, Serratia, Penicillium, Candida, and the like. To enhance productivity, strains of microorganisms are employed which have been isolated from nature and artificial variants thereof. Moreover, various technologies have been disclosed which increase the production of L-amino acids, such as recombinant DNA technology.
Methanol is an economical and commercially available raw material used in the conventional fermentation methods of carboxylic acid. Microorganisms employed in such methods include those belonging to the genera Achromobacter, Pseudomonas (Japanese Patent Application Publication No. Showa 45-25273), Protaminobacter (Japanese Patent Publication No. Showa 49-125590), Protaminobacter, Methanomonas (Japanese Patent Application Publication No. Showa 50-25790), Microcyclus (Japanese Patent Application Publication No. Showa 52-18886), Methylobacillus (Japanese Patent Application Publication No. Heisei 4-91793), and Bacillus (Japanese Patent Application Publication No. Heisei 3-505284).
Thus far, the use of artificial mutations or recombinant DNA techniques have been developed and used in a method of producing L-amino acids using Methylophilus bacteria. Specifically, the enzymatic activities of dihydrodipicolinate synthase and/or aspartokinase were increased (International Publication No. 00/61723). The amino acid export process has been a major obstacle in the production of amino acids by fermentation from methanol using methanol-assimilating bacteria. To overcome this problem, a mutant of the LysE protein, which participates in the export of L-lysine, exhibits L-lysine export activity in methanol-assimilating bacteria, and was isolated from bacteria of the genus Corynebacterium. Therefore, by breeding using artificial mutations, recombinant DNA techniques, and this modified L-lysine export carrier, it is possible to efficiently produce L-lysine. Hence, a method for producing L-amino acid using bacteria of the genus Methylophilus was developed (International Publication No. 00/61723 and Japanese Patent Publication No. 2004-166594).
Through the breeding of microorganisms such as discussed above, the ability to produce substances using methanol-assimilating bacteria has been greatly improved. However, there is still a need for the development of inexpensive and efficient methods of producing carboxylic acids from methanol.